Schistosomiasis is a disease caused by the parasitism of adult schistosomes in the veins and is broadly classified into urogenital schistosomiasis and intestinal schistosomiasis. An example of the urogenital schistosomiasis is schistosomiasis haematobia (pathogen: Schistosoma haematobium) and examples of the intestinal schistosomiasis include schistosomiasis mansoni (pathogen: S. mansoni), schistosomiasis mekongi (pathogen: S. mekongi), and schistosomiasis intercalatum (pathogen: S. intercalatum) as well as schistosomiasis japonica (pathogen: S. japonicum). Infection of humans with schistosomes occurs when the humans go into fresh water, for example, a river, a lake, or a marsh. The World Health Organization estimates that 200,000,000 people suffer from the disease worldwide, and the number of people died of severe complications associated with the disease is estimated to be annually 20,000 or 200,000, which varies from report to report. Schistosomiasis haematobia is distributed in Middle East, wide range of areas in Africa including Madagascar, and Mauritius, and schistosomiasis mansoni is distributed in, for example, the Arabian Peninsula, most of African countries located north of the equator (Egypt, Libya, Sudan, Somalia, Mali, and Senegal), Mauritius, Brazil, some of various Caribbean countries, Surinam, and Venezuela. Schistosomiasis japonica is distributed in, for example, the Yangtze valley in China, Philippines, and the island of Sulawesi in Indonesia, schistosomiasis mekongi is distributed in the Mekong river basin in Cambodia and Laos, and schistosomiasis intercalatum is locally distributed in West and Central Africa.
Also in Japan, there were several areas endemic for schistosomiasis japonica in the past. However, the execution of an eradication project including land-use alteration and measures for intermediate hosts as well as community education and mass examination has contributed to a drastic decrease in the number of infected people. As a result, there has been no report on people newly infected with Schistosoma japonicum since 1976 in Japan.
Information about the kinds of pathogens, life cycles of pathogens, clinical symptoms of infectious diseases, pathological diagnosis, and the like for schistosomiasis is described in detail in the homepage of Infectious Disease Surveillance Center, National Institute of Infectious Diseases (http://idsc.nih.go.jp/idwr/kansen/k06/k06—41/k06—41.html) (Non Patent Literature 1).
s for measures against schistosomiasis, instructions for the prophylaxis of infection have been made to avoid going barefoot into the habitat of shellfish as an intermediate host for schistosomes, i.e., a river, a pond, etc., and besides, praziquantel (Bayer Yakuhin) is commercially available as a magic bullet (Non Patent Literature 2). The treatment of schistosomiasis is basically conducted by single-dose administration of praziquantel at 40 mg/kg. It is said that schistosomiasis is cured by the treatment inmost cases. Acute symptoms (e.g., abdominal pain, diarrhea, mucous and bloody stool, fever, and cough) of schistosomiasis are known as Katayama's fever, and when not being treated, the symptoms are basically relieved and become chronic. Even when Katayama's fever is relieved by the administration of praziquantel, praziquantel is not effective against immature schistosomes, and is therefore recommended to be administered again after 3 months. Praziquantel is also said to have no prophylactic effect. Meanwhile, Non Patent Literature 1 also describes that it has been reported that artemether, which is one of artemisinin-based drugs serving as antimalarial drugs, exhibits an effect on schistosomes at the immature stage and may therefore be used not only as a therapeutic drug at the early stage of infection but also for the prophylaxis of the infection, but that artemether still remains unpopular. See FIG. 1 for a life cycle of schistosomes and effective administration periods of reported existing drugs.
Even when schistosomiasis is cured by the administration of praziquantel, once one suffers from liver dysfunction, the restoration is difficult and liver dysfunction is accumulated through repetitive infections. In Japan, as mentioned above, Schistosoma japonicum in the country was able to be eradicated by the prevention of infection from Oncomelania nosophora as an intermediate host for schistosomes and the early detection and treatment of patients. In contrast, wide infected areas remain in, for example, China, Southeast Asia, and Africa, and reports on the occurrence of resistance to praziquantel also exist. There is no prophylactic means such as a vaccine at present. Accordingly, there is also an international demand for the development of a novel antischistosomal agent which may also serve as a prophylactic drug.
[Non Patent Literature 1] http://idsc.nih.go.jp/idwr/kansen/k06/k06—41/k06—41.html
[Non Patent Literature 2] Prescription Drug Package Insert: praziquantel formulation (Biltricide® tablet) manufactured and sold by Bayer Yakuhin, Ltd. (revised in April, 2005)